1998 APA Report, Part III

(This is the third in a series of reports summarizing research presented at the American Psychiatric Association meeting in Toronto. Part I appeared in the August issue, and Part II in the September issue-Ed.)

Atypical antipsychotic treatment for borderline personality disorder (BPD) and augmentation therapy with olanzapine (Zyprexa) or estrogen replacement therapy (ERT) for patients with mood disorders were among the research questions addressed at the American Psychiatric Association's annual meeting in Toronto. Following are some brief reports of selected presentations.

Renal Function in Response to Lithium Administration

Because of the existing reports of patients who are experiencing renal failure while being treated with lithium (Eskalith, Lithobid), there exists guarded concern about the administration of lithium. To gauge the frequency of clinically significant changes in renal function during lithium maintenance and to examine potential risk factors, a chart review was conducted at Massachusetts General Hospital in Boston.

Patients treated with lithium for three or more years were targeted by the investigators. The gathered data allowed the determination of change from baseline creatinine at three-year intervals. They evaluated whether a significant change in creatinine (0.2 mg/dL)² in the first three years was correlated with further increases in creatinine from three to six years.

Of the 79 patients who were treated with lithium for three or more years (17 were treated for nine or more years), 27 had a significant increase in creatinine. A Spearman's rank correlation was used to examine the relationship between significant changes in creatinine in the first three years with changes from three to six years.
There was no specific relationship identified (r=-.068; p=0.67). A larger sample population is needed to examine whether significant changes in creatinine by year 3 are correlated with changes at six years to nine years, and nine years to 12 years (Demopulos CM et al., New Research 38).

Repetitive Transcranial Magnetic Stimulation Versus ECT for MDD

Researchers at Chaim Sheba Medical Center in Israel conducted a study to compare the efficacy and the side effects of repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) for patients with major depressive disorder.

Twenty patients were randomized to two groups and treated with either (rTMS or ECT. Severe major depression was diagnosed in all patients as measured by the 21-item Hamilton Depression Rating Scale (HAM-D-21>20). The HAM-D, Brief Psychiatric Rating Scale (BPRS), Pittsburgh Sleep Quality Index (PSQI), Global Assessment Scale (GAS) and Global Depression Rating (GDR) were used for evaluation at baseline and at the end of the second and fourth weeks of treatment. Up to 20 rTMS sessions were administered with a magstim rapid machine to the left prefrontal region of the head, and given at 90% of motor threshold.

During each session, 20 two-second trains at 10 Hz frequency, with a 45-second interval between trains, were administered. ECT was given following the guidelines of the American Psychiatric Association. Seizure threshold was determined at baseline, and consecutive treatment was administered at 2.5 times baseline energy. Electrode placement was unilateral at baseline in all cases. Cases that responded slowly to ECT were switched to bilateral placement from the seventh treatment.

ANOVA (analysis with variance) with repeated measures comparing baseline and week 4 clinical ratings for the HAM-D (f:19.9, p<0.0001), BPRS (f:12.3,p<0.0001), PSQI (f:10.5, p<0.0003), GDR (f:16.9, p<0.0001), and GAS (f:24, p<0.0001) demonstrated significant effect of treatment. However, a group effect was not observed. Therefore, it appears that ECT and rTMS have similar degrees of efficacy in dissolving depressive symptoms (Dannon PN et al., New Research 44).

Fluvoxamine and Enuresis in Children and Adolescents

Antienuretic properties are present in tricyclic antidepressants, but they are not regularly used in children because of their side effect profile. The selective serotonin reuptake inhibitors (SSRIs) have antidepressant properties similar to the tricyclics, but they are safer for use in children.

Investigators at the Tel Aviv Community Mental Health Center in Israel evaluated the efficacy of fluvoxamine (Luvox) and its antienuretic properties in children and adolescents. Nine children, ages 9 to 14, participated in the study. All of the patients had primary enuresis that was resistant to behavioral therapy. They were treated with fluvoxamine, 75 mg/day to 100 mg/day. Four patients received fluvoxamine purely to relieve their enuresis, while the remaining five received it for other primary indications. Enuresis was monitored daily, and mean voiding frequency was compared between three phases: baseline, on treatment and off treatment.
Treatment with fluvoxamine had no statistically significant effect on enuresis. However, a decrease in voiding frequency was observed in three children on fluvoxamine treatment. Thus, the researchers concluded that fluvoxamine does not contain significant antienuretic properties. They suggested that the combination of serotonergic with anticholinergic activity is a major factor in the antienuretic activity. When treating children or adolescents with obsessive-compulsive disorder and comorbid enuresis, clomipramine (Anafranil) is a more effective method of pharmacotherapy than fluvoxamine (Toren P et al., New Research 46).

Risperidone for Treatment of Dementia and Risk of Tardive Dyskinesia

A multicenter, double-blind study was conducted in 625 institutionalized dementia patients (73% with Alzheimer's disease, 15% with vascular dementia, 12% with mixed dementia) to evaluate the efficacy and safety of risperidone (Risperdal). Patients were randomly assigned to receive placebo or 0.5 mg/day, 1 mg/day or 2 mg/day of risperidone for 12 weeks.

According to scores on the Behavior Pathology in Alzheimer's Disease Rating Scale and the Cohen-Mansfield Agitation Inventory, significantly greater improvements were seen in psychosis and in the frequency and severity of aggressive behaviors in patients receiving 1 mg/day or 2 mg/day of risperidone than those receiving placebo. The frequency of adverse events, including extrapyramidal symptoms, was similar in patients receiving risperidone at 1 mg/day and placebo.

Two hundred and sixteen of the patients are participating in a one-year, open-label follow-up study. To date (May 1998), they have been exposed to risperidone for a mean ( SD) of 184128 days (69% have been exposed >90 days). No cases of tardive dyskinesia have been reported, and the patients show improvement on five measures of dyskinesia: dyskinetic movements, hyperkinesia, buccolinguomasticatory factor, choreoathetoid movements and clinical global impression of dyskinesia (Brecher MB, New Research 342).

Lesser Susceptibility to Nicotine in Patients with Parkinson's Disease

Substantial loss of nicotinic receptors in patients with Parkinson' disease (PD) has been demonstrated in postmortem studies. This may account for some of the cognitive, motoric and behavioral deficits seen in PD patients.

Epidemiologic studies have suggested that cigarette smoking is a strong negative risk factor for the development of PD. Blockade of central nicotinic receptors has been shown to produce cognition impairment in areas of new learning, short-term memory and psychomotor slowing, with increasing dose sensitivity with age and disease.

Studies of acute stimulation of nicotinic receptors in Alzheimer's disease with nicotine and the novel agonist ABT-418 have shown improvement in several measures of cognitive function. Prior studies of the effects of nicotine in PD have suggested some improvements in clinical symptomatology.

Quantitative dose-ranging studies of both acute and chronic nicotine in PD, to assess cognitive and motor effects in nine nondemented subjects with early to moderate PD, have been done. The subjects were given intravenous nicotine up to 125 µg/kg/min, followed by chronic administration of nicotine by transdermal patch with doses ranging up to 14 mg/day for two weeks. Testing occurred both during drug administration and up to two months after drug cessation for prolonged effects.

Preliminary analysis showed improvements after acute nicotine in stimulation in several areas of cognitive performance, particularly measures such as reaction time, central processing speed and decreased tracking error; improvements in attention and semantic retrieval were not seen. After chronic nicotine stimulation, improvements were seen in several motor measures, suggesting improved extrapyramidal functioning. This appeared to be sustained up to one month after drug discontinuation. Treatment was well tolerated, suggesting that nicotine stimulation may improve both cognitive and motor aspects of PD (Newhouse PA et al., New Research 356).